Author(s): Wang GL, Jiang BH, Rue EA, Semenza GL
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Abstract Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1\% O2 and decayed rapidly upon return of the cells to 20\% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.
This article was published in Proc Natl Acad Sci U S A
and referenced in Pediatrics & Therapeutics